Central Nucleus Of The Inferior Colliculus Research Articles

Obliteration of a glycinergic projection to the medial geniculate in an animal model of autism.

Auditory dysfunction affects the vast majority of people with autism spectrum disorder (ASD) and can range from deafness to hypersensitivity. In utero exposure to the antiepileptic valproic acid (VPA) is associated with significant risk of an ASD diagnosis in humans and timed in utero exposure to VPA is utilized as an animal model of ASD. VPA-exposed rats have significantly fewer neurons in their auditory brainstem, thalamus and cortex, reduced ascending projections to the midbrain and thalamus and reduced descending projections from the cortex to the auditory midbrain. Consistent with these anatomical changes, VPA-exposed animals also have abnormal auditory brainstem responses. We have recently described a significant ascending projection from calbindin-positive neurons in the medial nucleus of the trapezoid body (MNTB) to the ventral division of the medial geniculate (vMG) in rats that bypasses the central nucleus of the inferior colliculus (CNIC). Since we found that axonal projections to the vMG in VPA-exposed rats are reduced beyond what is predicted from neuron loss alone, we hypothesize that VPA exposure would result in a significant reduction in the MNTB projection to the vMG. We examined this hypothesis by quantifying the proportion of retrogradely-labeled neurons in the MNTB of control and VPA-exposed animals after injections of retrograde tracers in the CNIC and vMG in control and VPA-exposed animals. Our results indicate that in control animals, the MNTB forms the largest projection from the superior olivary complex to the MG and that this projection is nearly abolished by in utero VPA exposure.

Heterogeneous spatial tuning in the auditory pathway of the Mongolian Gerbil (Meriones unguiculatus).

Sound-source localization is based on spatial cues arising due to interactions of sound waves with the torso, head and ears. Here, we evaluated neural responses to free-field sound sources in the central nucleus of the inferior colliculus (CIC), the medial geniculate body (MGB) and the primary auditory cortex (A1) of Mongolian gerbils. Using silicon probes we recorded from anaesthetized gerbils positioned in the centre of a sound-attenuating, anechoic chamber. We measured rate-azimuth functions (RAFs) with broad-band noise of varying levels presented from loudspeakers spanning 210° in azimuth and characterized RAFs by calculating spatial centroids, Equivalent Rectangular Receptive Fields (ERRFs), steepest slope locations and spatial-separation thresholds. To compare neuronal responses with behavioural discrimination thresholds from the literature we performed a neurometric analysis based on signal-detection theory. All structures demonstrated heterogeneous spatial tuning with a clear dominance of contralateral tuning. However, the relative amount of contralateral tuning decreased from the CIC to A1. In all three structures spatial tuning broadened with increasing sound-level. This effect was strongest in CIC and weakest in A1. Neurometric spatial-separation thresholds compared well with behavioural discrimination thresholds for locations directly in front of the animal. Our findings contrast with those reported for another rodent, the rat, which exhibits homogenous and sharply delimited contralateral spatial tuning. Spatial tuning in gerbils resembles more closely the tuning reported in A1 of cats, ferrets and non-human primates. Interestingly, gerbils, in contrast to rats, share good low-frequency hearing with carnivores and non-human primates, which may account for the observed spatial tuning properties.

Midbrain sensitivity to auditory motion studied with dichotic sweeps of broadband noise

Many neurons in the central nucleus of the inferior colliculus (IC) show sensitivity to interaural time differences (ITDs), which is thought to be relayed from the brainstem. However, studies with interaural phase modulation of pure tones showed that IC neurons have a sensitivity to changes in ITD that is not present at the level of the brainstem. This sensitivity has been interpreted as a form of sensitivity to motion.A new type of stimulus is used here to study the sensitivity of IC neurons to dynamic changes in ITD, in which broad- or narrowband stimuli are swept through a range of ITDs with arbitrary start-ITD, end-ITD, speed, and direction. Extracellular recordings were obtained under barbiturate anesthesia in the cat. We applied the same analyses as previously introduced for the study of responses to tones.We find effects of motion which are similar to those described in response to interaural phase modulation of tones. The size of the effects strongly depended on the motion parameters but was overall smaller than reported for tones. We found that the effects of motion could largely be explained by the temporal response pattern of the neuron such as adaptation and build-up. Our data add to previous evidence questioning true coding of motion at the level of the IC.

Medial superior olive in the rat: Anatomy, sources of input and axonal projections

Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential aspect of binaural hearing: the ability of animals to localize the sources of low-frequency sounds by detecting the interaural time difference (ITD), that is the difference in the time at which the sound arrives at each ear. In mammals, ITDs are mostly encoded in the medial superior olive (MSO), one of the main nuclei of the superior olivary complex (SOC). Because of their small heads and high frequency hearing range, rats and mice are often considered unable to use ITDs for sound localization. Moreover, their MSO is frequently viewed as too small or insignificant compared to that of mammals that use ITDs to localize sounds, including cats and gerbils. However, recent research has demonstrated remarkable similarities between most morphological and physiological features of mouse MSO neurons and those of MSO neurons of mammals that use ITDs. In this context, we have analyzed the structure and neural afferent and efferent connections of the rat MSO, which had never been studied by injecting neuroanatomical tracers into the nucleus.The rat MSO spans the SOC longitudinally. It is relatively small caudally, but grows rostrally into a well-developed column of stacked bipolar neurons. By placing small, precise injections of the bidirectional tracer biotinylated dextran amine (BDA) into the MSO, we show that this nucleus is innervated mainly by the most ventral and rostral spherical bushy cells of the anteroventral cochlear nucleus of both sides, and by the most ventrolateral principal neurons of the ipsilateral medial nucleus of the trapezoid body. The same experiments reveal that the MSO densely innervates the most dorsolateral region of the central nucleus of the inferior colliculus, the central region of the dorsal nucleus of the lateral lemniscus, and the most lateral region of the intermediate nucleus of the lateral lemniscus of its own side. Therefore, the MSO is selectively innervated by, and sends projections to, neurons that process low-frequency sounds. The structural and hodological features of the rat MSO are notably similar to those of the MSO of cats and gerbils. While these similarities raise the question of what functions other than ITD coding the MSO performs, they also suggest that the rat MSO is an appropriate model for future MSO-centered research.

Motor, somatosensory, and executive cortical areas elicit monosynaptic and polysynaptic neuronal activity in the auditory midbrain

We recently reported that the central nucleus of the inferior colliculus (the auditory midbrain) is innervated by glutamatergic pyramidal cells originating not only in auditory cortex (AC), but also in multiple ‘non-auditory’ regions of the cerebral cortex. Here, in anaesthetised rats, we used optogenetics and electrical stimulation, combined with recording in the inferior colliculus to determine the functional influence of these descending connections. Specifically, we determined the extent of monosynaptic excitation and the influence of these descending connections on spontaneous activity in the inferior colliculus.A retrograde virus encoding both green fluorescent protein (GFP) and channelrhodopsin (ChR2) injected into the central nucleus of the inferior colliculus (ICc) resulted in GFP expression in discrete groups of cells in multiple areas of the cerebral cortex. Light stimulation of AC and primary motor cortex (M1) caused local activation of cortical neurones and increased the firing rate of neurones in ICc indicating a direct excitatory input from AC and M1 to ICc with a restricted distribution. In naïve animals, electrical stimulation at multiple different sites within M1, secondary motor, somatosensory, and prefrontal cortices increased firing rate in ICc. However, it was notable that stimulation at some adjacent sites failed to influence firing at the recording site in ICc. Responses in ICc comprised singular spikes of constant shape and size which occurred with a short, and fixed latency (∼ 5 ms) consistent with monosynaptic excitation of individual ICc units. Increasing the stimulus current decreased the latency of these spikes, suggesting more rapid depolarization of cortical neurones, and increased the number of (usually adjacent) channels on which a monosynaptic spike was seen, suggesting recruitment of increasing numbers of cortical neurons. Electrical stimulation of cortical regions also evoked longer latency, longer duration increases in firing activity, comprising multiple units with spikes occurring with significant temporal jitter, consistent with polysynaptic excitation. Increasing the stimulus current increased the number of spikes in these polysynaptic responses and increased the number of channels on which the responses were observed, although the magnitude of the responses always diminished away from the most activated channels. Together our findings indicate descending connections from motor, somatosensory and executive cortical regions directly activate small numbers of ICc neurones and that this in turn leads to extensive polysynaptic activation of local circuits within the ICc.

Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus.

Cholinergic signaling shapes sound processing and plasticity in the inferior colliculus (IC), the midbrain hub of the central auditory system, but how cholinergic terminals contact and influence individual neuron types in the IC remains largely unknown. Using pharmacology and electrophysiology, we recently found that acetylcholine strongly excites VIP neurons, a class of glutamatergic principal neurons in the IC, by activating α3β4* nicotinic acetylcholine receptors (nAChRs). Here, we confirm and extend these results using tissue from mice of both sexes. First, we show that mRNA encoding α3 and β4 nAChR subunits is expressed in many neurons throughout the IC, including most VIP neurons, suggesting that these subunits, which are rare in the brain, are important mediators of cholinergic signaling in the IC. Next, by combining fluorescent labeling of VIP neurons and immunofluorescence against the vesicular acetylcholine transporter (VAChT), we show that individual VIP neurons in the central nucleus of the IC (ICc) are contacted by a large number of cholinergic boutons. Cholinergic boutons were distributed adjacent to the somata and along the full length of the dendritic arbors of VIP neurons, positioning cholinergic signaling to affect synaptic computations arising throughout the somatodendritic compartments of VIP neurons. In addition, cholinergic boutons were occasionally observed in close apposition to dendritic spines on VIP neurons, raising the possibility that cholinergic signaling also modulates presynaptic release onto VIP neurons. Together, these results strengthen the evidence that cholinergic signaling exerts widespread influence on auditory computations performed by VIP neurons and other neurons in the IC.

Leveling up: a long-range olivary projection to the medial geniculate without collaterals to the central nucleus of the inferior colliculus in rats.

The medial nucleus of the trapezoid body (MNTB) is one of the monaural cell groups situated within the superior olivary complex (SOC), a constellation of brainstem nuclei with numerous roles in hearing. Principal MNTB neurons are glycinergic and express the calcium-binding protein, calbindin (CB). The MNTB receives its main glutamatergic, excitatory input from the contralateral cochlear nucleus via the calyx of Held and converts this into glycinergic inhibition directed toward nuclei in the SOC and the ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL). Through this inhibition, the MNTB plays essential roles in localization of sound sources and encoding spectral and temporal features of sound. In rats, very few MNTB neurons project to the inferior colliculus. However, our recent study of SOC projections to the auditory thalamus revealed a substantial number of retrogradely labeled MNTB neurons. This observation led us to examine whether the rat MNTB provides a long-range projection to the medial geniculate body (MGB). We examined this possible projection using retrograde and anterograde tract tracing and immunohistochemistry for CB and the glycine receptor. Our results demonstrate a significant projection to the MGB from the ipsilateral MNTB that does not involve a collateral projection to the inferior colliculus.

Brain Mapping the Effects of Chronic Aerobic Exercise in the Rat Brain Using FDG PET

Exercise is a key component to health and wellness and is thought to play an important role in brain activity. Changes in brain activity after exercise have been observed through various neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). The precise impact of exercise on brain glucose metabolism (BGluM) is still unclear; however, results from PET studies seem to indicate an increase in regional metabolism in areas related to cognition and memory, direction, drive, motor functions, perception, and somatosensory areas in humans. Using PET and the glucose analog [18F]-Fluorodeoxyglucose (18F-FDG), we assessed the changes in BGluM between sedentary and chronic exercise in rats. Chronic treadmill exercise treatment demonstrated a significant increase in BGluM activity in the following brain regions: the caudate putamen (striatum), external capsule, internal capsule, deep cerebellar white matter, primary auditory cortex, forceps major of the corpus callosum, postsubiculum, subiculum transition area, and the central nucleus of the inferior colliculus. These brain regions are functionally associated with auditory processing, memory, motor function, and motivated behavior. Therefore, chronic daily treadmill running in rats stimulates BGluM in distinct brain regions. This identified functional circuit provides a map of brain regions for future molecular assessment which will help us understand the biomarkers involved in specific brain regions following exercise training, as this is critical in exploring the therapeutic potential of exercise in the treatment of neurodegenerative disease, traumatic brain injury, and addiction.

Bilateral Interactions in the Mouse Dorsal Inferior Colliculus Enhance the Ipsilateral Neuronal Responses and Binaural Hearing.

The inferior colliculus (IC) is a critical centre for the binaural processing of auditory information. However, previous studies have mainly focused on the central nucleus of the inferior colliculus (ICC), and less is known about the dorsal nucleus of the inferior colliculus (ICD). Here, we first examined the characteristics of the neuronal responses in the mouse ICD and compared them with those in the inferior colliculus under binaural and monaural conditions using in vivo loose-patch recordings. ICD neurons exhibited stronger responses to ipsilateral sound stimulation and better binaural summation than those of ICC neurons, which indicated a role for the ICD in binaural hearing integration. According to the abundant interactions between bilateral ICDs detected using retrograde virus tracing, we further studied the effect of unilateral ICD silencing on the contralateral ICD. After lidocaine was applied, the responses of some ICD neurons (13/26), especially those to ipsilateral auditory stimuli, decreased. Using whole-cell recording and optogenetic methods, we investigated the underlying neuronal circuits and synaptic mechanisms of binaural auditory information processing in the ICD. The unilateral ICD provides both excitatory and inhibitory projections to the opposite ICD, and the advantaged excitatory inputs may be responsible for the enhanced ipsilateral responses and binaural summation of ICD neurons. Based on these results, the contralateral ICD might modulate the ipsilateral responses of the neurons and binaural hearing.

Comparing frequency-chirp sensitivity in the inferior colliculus to basic response properties using novel stimuli

Most neurons in the central nucleus of the inferior colliculus (ICC) are sensitive to the direction of phase-curvature of Schroeder-phase (SCHR) stimuli. This phase-curvature controls the direction and velocity of frequency chirps within the fundamental SCHR period. Differences in responses to different SCHR stimuli may originate from an underlying sensitivity to frequency chirp direction or velocity. However, known ICC sensitivities, such as those to frequency or envelope periodicity and duty cycle, may also contribute to the observed effect. To parse these confounding SCHR stimulus features, we designed novel frequency-chirping stimuli to isolate the influences of periodicity, duty cycle, and frequency-chirp direction or velocity on ICC neuron responses. Extracellular, single-unit recordings of chirp responses were made in awake rabbit ICC. Simultaneously, basic response properties were characterized using methods such as frequency response maps, modulation transfer functions, and spectro-temporal receptive fields. By comparing basic response properties across chirp-sensitive neurons (comprising 80% of ICC neurons), we can outline the shared characteristics among them. Our goal is to determine whether frequency-chirp sensitivity in ICC neurons is independent of other established feature sensitivities. Frequency-chirp-sensitive neurons are interesting, because they may play a unique role in encoding sounds with complex phase, including speech. [Work supported by NIDCD-R01-001641.]

The Untouchable Ventral Nucleus of the Trapezoid Body: Preservation of a Nucleus in an Animal Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by repetitive behaviors, poor social skills, and difficulties with communication and hearing. The hearing deficits in ASD range from deafness to extreme sensitivity to routine environmental sounds. Previous research from our lab has shown drastic hypoplasia in the superior olivary complex (SOC) in both human cases of ASD and in an animal model of autism. However, in our study of the human SOC, we failed to find any changes in the total number of neurons in the ventral nucleus of the trapezoid body (VNTB) or any changes in cell body size or shape. Similarly, in animals prenatally exposed to the antiepileptic valproic acid (VPA), we failed to find any changes in the total number, size or shape of VNTB neurons. Based on these findings, we hypothesized that the neurotransmitter profiles, ascending and descending axonal projections of the VNTB are also preserved in these neurodevelopmental conditions. We investigated this hypothesis using a combination of immunohistochemistry and retrograde tract tracing. We found no difference between control and VPA-exposed animals in the number of VNTB neurons immunoreactive for choline acetyltransferase (ChAT). Additionally, we investigated the ascending projections from the VNTB to both the central nucleus of the inferior colliculus (CNIC) and medial geniculate (MG) and descending projections to the cochlea. Our results indicate no significant differences in the ascending and descending projections from the VNTB between control and VPA-exposed animals despite drastic changes in these projections from surrounding nuclei. These findings provide evidence that certain neuronal populations and circuits may be protected against the effects of neurodevelopmental disorders.

Different binaural processing of the envelope component and the temporal fine structure component of a narrowband noise in rat inferior colliculus

Complex broadband sounds are decomposed by peripheral auditory filters into a series of relatively narrowband signals, each with a slowly varying envelope (ENV) and a rapidly fluctuating temporal fine structure (TFS). ENV and TFS information at the bilateral ears contribute differentially to auditory perception. However, whether the difference could attribute to mechanisms of binaural integration remains an open question. As a potential neural correlate, subsets of neurons in the central nucleus of the inferior colliculus (ICC) are known to integrate binaural information with binaural inhibition or binaural summation. Therefore, we recorded the frequency-following responses (FFRs) to the ENV and TFS components of narrowband noises in the ICC of anesthetized rats and examined changes in FFR amplitude and stimulus-response coherence under various sound-delivery settings. We showed that binaural FFRENV was predominantly elicited by contralateral inputs and inhibited by ipsilateral inputs, exhibiting a “binaural-inhibition” like property. On the other hand, binaural FFRTFS received a balanced contribution from both sides, echoing the “binaural-summation” mechanism. What is more, binaural FFRENV was significantly correlated with contralateral-evoked but not ipsilateral-evoked FFRENV, while binaural FFRTFS correlated with both contralateral- and ipsilateral-evoked FFRTFS. Overall, these results suggest distinct binaural processing of ENV and TFS information at the midbrain level.

Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation

Optical stimulation is a paradigm-shifting approach to modulating neural activity that has the potential to overcome the issue of current spread that occurs with electrical stimulation by providing focused stimuli. But optical stimulation either requires high power infrared light or genetic modification of neurons to make them responsive to lower power visible light. This work examines optical activation of auditory neurons following optogenetic modification via AAV injection in two species (mouse and guinea pig). An Anc80 viral vector was used to express the channelrhodopsin variant ChR2-H134R fused to a fluorescent reporter gene under the control of the human synapsin-1 promoter. The AAV was administered directly to the cochlea (n = 33) or posterior semi-circular canal of C57BL/6 mice (n = 4) or to guinea pig cochleae (n = 6). Light (488 nm), electrical stimuli or the combination of these (hybrid stimulation) was delivered to the cochlea via a laser-coupled optical fibre and co-located platinum wire. Activation thresholds, spread of activation and stimulus interactions were obtained from multi-unit recordings from the central nucleus of the inferior colliculus of injected mice, as well as ChR2-H134R transgenic mice (n = 4). Expression of ChR2-H134R was examined by histology. In the mouse, transduction of auditory neurons by the Anc80 viral vector was most successful when injected at a neonatal age with up to 89% of neurons transduced. Auditory neuron transductions were not successful in guinea pigs. Inferior colliculus responses to optical stimuli were detected in a cochleotopic manner in all mice with ChR2-H134R expression. There was a significant correlation between lower activation thresholds in mice and higher proportions of transduced neurons. There was no difference in spread of activation between optical stimulation and electrical stimulation provided by the light/electrical delivery system used here (optical fibre with bonded 25 µm platinum/iridium wire). Hybrid stimulation, comprised of sub-threshold optical stimulation to ‘prime’ or raise the excitability of the neurons, lowered the threshold for electrical activation in most cases, but the impact on excitation width was more variable compared to transgenic mice. This study demonstrates the impact of opsin expression levels and expression pattern on optical and hybrid stimulation when considering optical or hybrid stimulation techniques for neuromodulation.

Neonatal exposure to monosodium glutamate results in impaired auditory brainstem structure and function

Excitotoxic injury during the neonatal period has been shown to result in neurodegenerative changes in several different brain regions. Exposure to monosodium glutamate (MSG) during the first two postnatal weeks results in glutamate neurotoxicity in the cochlea and has been shown to result in damage to cochlear hair cells and fewer neurons in the spiral ganglion. Further, we have shown that such exposure results in fewer neurons in the cochlear nucleus and superior olivary complex and abnormal expression of the calcium binding proteins calbindin and calretinin. Based on these findings, we hypothesized that neonatal MSG exposure would result in loss of neurons at more rostral levels in the auditory brainstem, and this exposure would result in abnormal brainstem auditory evoked potentials. We identified a significantly lower density of neurons in the spiral ganglion, heterogenous loss of neurons in the globular bushy cell-trapezoid body circuit, and fewer neurons in the nuclei of the lateral lemniscus and central nucleus of the inferior colliculus. The most severe loss of neurons was found in the inferior colliculus. Click-evoked auditory brainstem responses revealed significantly higher thresholds and longer latency responses, but these did not deteriorate with age. These results, together with our previous findings, indicate that neonatal exposure to MSG results in fewer neurons throughout the entire auditory brainstem and results in abnormal auditory brainstem responses.

Excitatory cholecystokinin neurons of the midbrain integrate diverse temporal responses and drive auditory thalamic subdomains

The central nucleus of the inferior colliculus (ICC) integrates information about different features of sound and then distributes this information to thalamocortical circuits. However, the lack of clear definitions of circuit elements in the ICC has limited our understanding of the nature of these circuit transformations. Here, we combine virus-based genetic access with electrophysiological and optogenetic approaches to identify a large family of excitatory, cholecystokinin-expressing thalamic projection neurons in the ICC of the Mongolian gerbil. We show that these neurons form a distinct cell type, displaying uniform morphology and intrinsic firing features, and provide powerful, spatially restricted excitation exclusively to the ventral auditory thalamus. In vivo, these neurons consistently exhibit V-shaped receptive field properties but strikingly diverse temporal responses to sound. Our results indicate that temporal response diversity is maintained within this population of otherwise uniform cells in the ICC and then relayed to cortex through spatially restricted thalamic subdomains.

Abnormal morphology and subcortical projections to the medial geniculate in an animal model of autism.

Auditory dysfunction, including hypersensitivity and tinnitus, is a common symptom of autism spectrum disorder (ASD). Prenatal exposure to the antiseizure medication valproic acid (VPA) significantly increases the risk of ASD in humans and similar exposure is utilized as an animal model of ASD in rodents. Animals exposed to VPA in utero have abnormal activity in their auditory cortex in response to sounds, fewer neurons, abnormal neuronal morphology, reduced expression of calcium-binding proteins, and reduced ascending projections to the central nucleus of the inferior colliculus. Unfortunately, these previous studies of central auditory circuits neglect the medial geniculate (MG), which serves as an important auditory relay from the midbrain to the auditory cortex. Here, we examine the structure and connectivity of the medial geniculate (MG) in rats prenatally exposed to VPA. Our results indicate that VPA exposure results in significantly smaller and fewer neurons in the ventral and medial nuclei of the MG. Furthermore, injections of the retrograde tract tracer fluorogold (FG) in the MG result in significantly fewer FG+ neurons in the inferior colliculus, superior olivary complex, and ventral cochlear nucleus. Together, we interpret these findings to indicate that VPA exposure results in hypoplasia throughout the auditory circuits and that VPA has a differential impact on some long-range axonal projections from brainstem centers to the thalamus. Together, our findings support the widespread impact of VPA on neurons and sensory circuits in the developing brain.

Cortical Stimulation Induces Excitatory Postsynaptic Potentials of Inferior Colliculus Neurons in a Frequency-Specific Manner.

Corticofugal modulation of auditory responses in subcortical nuclei has been extensively studied whereas corticofugal synaptic transmission must still be characterized. This study examined postsynaptic potentials of the corticocollicular system, i.e., the projections from the primary auditory cortex (AI) to the central nucleus of the inferior colliculus (ICc) of the midbrain, in anesthetized C57 mice. We used focal electrical stimulation at the microampere level to activate the AI (ESAI) and in vivo whole-cell current-clamp to record the membrane potentials of ICc neurons. Following the whole-cell patch-clamp recording of 88 ICc neurons, 42 ICc neurons showed ESAI-evoked changes in the membrane potentials. We found that the ESAI induced inhibitory postsynaptic potentials in 6 out of 42 ICc neurons but only when the stimulus current was 96 μA or higher. In the remaining 36 ICc neurons, excitatory postsynaptic potentials (EPSPs) were induced at a much lower stimulus current. The 36 ICc neurons exhibiting EPSPs were categorized into physiologically matched neurons (n = 12) when the characteristic frequencies of the stimulated AI and recorded ICc neurons were similar (≤1 kHz) and unmatched neurons (n = 24) when they were different (>1 kHz). Compared to unmatched neurons, matched neurons exhibited a significantly lower threshold of evoking noticeable EPSP, greater EPSP amplitude, and shorter EPSP latency. Our data allow us to propose that corticocollicular synaptic transmission is primarily excitatory and that synaptic efficacy is dependent on the relationship of the frequency tunings between AI and ICc neurons.

Amygdala inhibition impairs fear conditioning but increases the stimulus-driven activity in the inferior colliculus

It has been shown that fear conditioning improves the steady-state evoked potentials driven by a long lasting amplitude modulated tone in the inferior colliculus. In this work we tested the hypothesis that the amygdala modulates this effect, since it plays a crucial role in assessing the biological relevance of environmental stimuli. We inhibited the basolateral nucleus of the amygdala of rats by injecting a GABAa receptor agonist (muscimol) before the recall test session of an auditory fear conditioning paradigm and recorded the evoked activity in the central nucleus of the inferior colliculus. According to our results, the treatment with muscimol decreased the expression of freezing behavior during the recall test session, but did not impair the entrainment of the evoked activity in the inferior colliculus induced by fear conditioning. We repeated the injection protocol with another group of rats but without pairing the tone to an aversive stimulus and observed that the inhibition of the basolateral amygdala enhances the stimulus-driven activity in the inferior colliculus regardless of the conditioning task. Our findings suggest that the basolateral amygdala exerts a tonic modulation over the encoding of sensory information at the early stages of the sensory pathway.

Postnatal exposure to an acoustically enriched environment alters the morphology of neurons in the adult rat auditory system

The structure of neurons in the central auditory system is vulnerable to various kinds of acoustic exposures during the critical postnatal developmental period. Here we explored long-term effects of exposure to an acoustically enriched environment (AEE) during the third and fourth weeks of the postnatal period in rat pups. AEE consisted of a spectrally and temporally modulated sound of moderate intensity, reinforced by a behavioral paradigm. At the age of 3-6months, a Golgi-Cox staining was used to evaluate the morphology of neurons in the inferior colliculus (IC), the medial geniculate body (MGB), and the auditory cortex (AC). Compared to controls, rats exposed to AEE showed an increased mean dendritic length and volume and the soma surface in the external cortex and the central nucleus of the IC. The spine density increased in both the ventral and dorsal divisions of the MGB. In the AC, the total length and volume of the basal dendritic segments of pyramidal neurons and the number and density of spines on these dendrites increased significantly. No differences were found on apical dendrites. We also found an elevated number of spines and spine density in non-pyramidal neurons. These results show that exposure to AEE during the critical developmental period can induce permanent changes in the structure of neurons in the central auditory system. These changes represent morphological correlates of the functional plasticity, such as an improvement in frequency tuning and synchronization with temporal parameters of acoustical stimuli.

Stimulus-frequency-dependent dominance of sound localization cues across the cochleotopic map of the inferior colliculus.

The horizontal direction of a sound source (i.e., azimuth) is perceptually determined in a frequency-dependent manner: low- and high-frequency sounds are localized via differences in the arrival time and intensity of the sound at the two ears, respectively, called interaural time and level differences (ITDs and ILDs). In the central auditory system, these binaural cues to direction are thought to be separately encoded by neurons tuned to low and high characteristic frequencies (CFs). However, at high sound levels a neuron often responds to frequencies far from its CF, raising the possibility that individual neurons may encode the azimuths of both low- and high-frequency sounds using both binaural cues. We tested this possibility by measuring auditory-driven single-unit responses in the central nucleus of the inferior colliculus (ICC) of unanesthetized female Dutch Belted rabbits with a multitetrode drive. At 70 dB SPL, ICC neurons across the cochleotopic map transmitted information in their firing rates about the direction of both low- and high-frequency noise stimuli. We independently manipulated ITD and ILD cues in virtual acoustic space and found that sensitivity to ITD and ILD, respectively, shaped the directional sensitivity of ICC neurons to low (<1.5 kHz)- and high (>3 kHz)-pass stimuli, regardless of the neuron's CF. We also found evidence that high-CF neurons transmit information about both the fine-structure and envelope ITD of low-frequency sound. Our results indicate that at conversational sound levels the majority of the cochleotopic map is engaged in transmitting directional information, even for sources with narrowband spectra.NEW & NOTEWORTHY A "division of labor" has previously been assumed in which the directions of low- and high-frequency sound sources are thought to be encoded by neurons preferentially sensitive to low and high frequencies, respectively. Contrary to this, we found that auditory midbrain neurons encode the directions of both low- and high-frequency sounds regardless of their preferred frequencies. Neural responses were shaped by different sound localization cues depending on the stimulus spectrum-even within the same neuron.